A 5 year in-vitro investigation of the mechanics of the natural mitral valve (MV) is proposed to continue our previous work examining normal valve mechanics, and changes that occur in cases of disease or following valve chemical fixation. The normal fluid and leaflet dynamics will be studied to examine the effects of annular planarity, and annular size on overall valve function. The relative changes in the fluid and leaflet mechanics will be assessed by measuring the transmitral flow directly, and the valve leaflet dynamics by high-speed video imaging, force measurements, and Doppler ultrasound. The hemodynamics and leaflet dynamics will be tied to leaflet tissue mechanics through a graphite marker tracking technique to assess the leaflet strain fields and flexure under dynamic conditions. This study will also address diseased states by examining a range of annular orifice areas along with planarity and altered papillary muscle (PM) position. Information regarding valvular function with respect to annular planarity will assist surgeons in critical decisions when performing valvular repair procedures, such as ring annuloplasty and chordal replacement. Further examination of chemical fixation techniques is also proposed to study static fixation processes. This will provide a better understanding of how structural modifications that occur during chemical fixation influence valve dynamics. The significance and clinical relevance of the proposed research is to improve our fundamental understanding of mitral valve function transmitral fluid mechanics and leaflet dynamics) under normal anatomical conditions and pathological changes to the mitral apparatus, especially due to the effects of chronic and acute ischemic mitral regurgitation. The goal is to enhance our understanding of valve dynamics through controlled in vitro MV testing under physiologic conditions by development of advanced in vitro modeling techniques. This will provide surgeons and cardiologists scientific data on the response of the MV to changes in annular planarity and size and PM positioning. This will result in improved diagnosis and treatment of MV disease by physicians, and provide surgeons information about the effect that repair techniques have on overall valve functionality. In the case of MV replacements, investigating fixation processes will help in their manufacture by providing data on valve dynamics following fixation. A comprehensive in vitro study utilizing both flexible and rigid left ventricular models and human and porcine mitral valves is planned. The experiments will be performed in a controlled environment providing isolation of specific parameters without artifacts introduced by competing factors. The use of state of the art measurement systems unavailable for in vivo use will yield significant results.